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HHS Public Access: The Effects of Cigarette Smoking On Male Fertility
HHS Public Access: The Effects of Cigarette Smoking On Male Fertility
HHS Public Access: The Effects of Cigarette Smoking On Male Fertility
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Postgrad Med. Author manuscript; available in PMC 2016 April 01.
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Abstract
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Cigarette smoking, one of the main causes of preventable morbidity and mortality, has a multitude
of well-known side effects. The relationship between cigarette smoking and infertility has been
studied for decades; however, large-scale, population-wide prospective studies are lacking. The
majority of the current literature is in the form of retrospective studies focused on the effects of
smoking on semen analyses. This article discusses the results of these studies and reviews the
postulated mechanisms. The effects of smoking on assisted reproduction and in vitro fertilization
outcomes are noted. The consequences of smoking while pregnant on future fertility as well as the
outcomes of second-hand smoke are analyzed. The current evidence suggests that men should be
advised to abstain from smoking in order to improve reproductive outcomes.
Keywords
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Introduction
It has been estimated that over one third of all men globally smoke some form of tobacco
and that 21.6% of American men smoke cigarettes.1 Smoking has been linked to a myriad of
adverse health outcomes, including cardiovascular disease, respiratory disease, and cancer of
the lungs, bladder, cervix, esophagus, kidney, pancreas, and stomach.2 More recently,
researchers have begun to explore the relationship between cigarette smoking and
reproductive health.
The American Society for Reproductive Medicine defines infertility as the inability to
achieve pregnancy following 12 months of regular, unprotected sexual intercourse.3 It has
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been estimated that up to 15% of all couples attempting to have children face some form of
infertility.4 Although almost half of all cases of infertility are due exclusively to female
Correspondence: Dr. Jason R. Kovac, MD, PhD, FRCSC, Male Reproductive Endocrinology and Surgery, 12188-A North Meridian
Street, Suite 200, Carmel, IN. Tel: 317-564-5100, jkovac@urologyin.com.
Financial and competing interests disclosure
Larry I Lipshultz is a consultant and member of the speakers’ bureaus of Auxilium, Lily, and Endo. Jason R Kovac is a National
Institutes of Health K12 Scholar supported by a Male Reproductive Health Research Career Development Physician-Scientist Award
(HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Program. The authors
have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Kovac et al. Page 2
factors, the male factor is the sole etiology in approximately 30% of couples. An additional
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20% of infertile couples have a combination of male and female factors. Thus, male factor
infertility plays a significant role in 50% of all couples with infertility.5 This review
examines the literature to elucidate the potential effects of cigarette smoking on male
infertility.
related links, and abstract summaries. Applicable studies were read and included in this
current review.
In another large cohort of 1786 men undergoing infertility workup (655 smokers and 1131
nonsmokers), Kunzle et al7 demonstrated that smoking was associated with decreases in
sperm density (15.3%), total sperm counts (17.5%), and total motile sperm (16.6%)
compared with nonsmokers. Furthermore, morphology (percent of normal forms) as well as
ejaculate volume was slightly affected by smoking but not to any significant degree. Effects
on ejaculate volume were found in a study by Saaranen et al,8 who noted smokers had lower
semen volumes per ejaculate than nonsmokers with a more specific inhibition occurring in
men who smoked > 16 cigarettes per day.
Several smaller studies have corroborated the aforementioned findings. Zhang et al9 studied
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362 Chinese men attending an infertility clinic and found that smokers demonstrated
decreased semen volumes, sperm concentrations, and rates of forward progression compared
with nonsmokers. The authors also examined the physiological basis for these changes by
testing seminal plasma levels of superoxide dismutase, which is an enzyme that participates
in the oxidative stress pathway and has been previously shown to be lower in the seminal
plasma of infertile men.10,11 Zhang et al found that superoxide dismutase levels were
inversely correlated with the amount and duration of cigarette smoking, suggesting a
relationship among smoking, oxidative stress, and infertility. Another study of 200 infertile
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men found higher rates of reduced sperm motility and abnormal sperm morphology among
smokers.12 Chia et al13 reported similar results in 618 Chinese men. Within the cohort
studied by Chia et al, the lower sperm concentrations and higher rates of abnormal sperm
morphology identified in smokers were also found to be dose dependent.
Merino and colleagues,14 who studied 358 Mexican men stratified into 3 categories based on
the number of cigarettes smoked per day, also confirmed this type of dose dependency. The
authors confirmed the effects of smoking on reduced sperm density and abnormal
morphology, but also extended these findings to note that men who smoked < 10 cigarettes
per day experienced significant changes in their semen analysis parameters. Therefore, even
“light” smokers appeared to be at risk for adverse effects on fertility.
Interestingly, some studies have failed to establish the relationship between cigarette
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smoking and adverse effects on semen parameters. The largest of these was a case-control
study of > 2000 British men being treated for infertility.15 Results from this study suggested
that smoking was not an independent risk factor for decreased concentrations of motile
sperm. However, additional sperm parameters, including sperm morphology, were not
assessed. Dikshit et al16 found that neither cigarette smoking nor chewing tobacco were
significant risk factors for impaired semen quality among 626 men presenting to infertility
clinics. Hassa and colleagues17 noted similar results in a cohort of 223 Turkish men.
Furthermore, when 889 men presenting for vasectomy were examined, no significant
differences in sperm density or motility were observed between smoking and nonsmoking
men.18 Of note, this particular study population was not drawn from patients presenting for
an evaluation of male infertility, in contrast to many of the aforementioned studies. Indeed,
men presenting for vasectomy can be presumed to be fertile, suggesting variable effects of
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smoking in men with infertility and those without. While highlighting the importance of
patient selection in examining the effects of smoking on fertility, these studies do suggest
that men with difficulty conceiving should be counseled to stop smoking in order to
optimize their fertility outcomes.
Liu et al21 examined the relationship between seminal zinc levels and semen parameters.
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The authors found that smokers had lower seminal zinc levels than nonsmokers, with
associated decreases in sperm concentration, motility, and morphology. Interestingly,
smokers with normal seminal zinc concentrations did not experience the same degree of
abnormal semen parameters as those smokers with decreased seminal zinc, suggesting that
zinc concentrations could play a role.
There is also evidence to suggest that the adverse effects of smoking may not be due
exclusively to the toxins found in cigarette smoke. Indeed, a study examining the effects of
oral nicotine on male rats found that rats exposed to oral nicotine experienced significant
decreases in sperm motility and sperm count.22 Thus, nicotine may also play an important
role in the adverse effects of smoking on fertility, independent of the toxins found in the
smoke. Interestingly, parameters affected by oral nicotine were improved following 30 days
of cessation, suggesting a component of reversibility to these effects. Furthermore, a study
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of 210 men suggested that men with higher cotinine concentrations in the seminal plasma
also had a greater percentage of abnormal sperm morphology.23 Because cotinine is a
metabolite of nicotine, these findings further the theory that nicotine itself may be a possible
driver of the adverse effects of smoking on fertility. Further studies are needed to determine
the exact role of nicotine in the pathogenesis of semen analysis and morphology changes.
assisted reproduction techniques demonstrated that couples in which the male partner
recently smoked had a significantly lower live birth rate with IVF or ICSI (7.8% vs 21.1% in
nonsmoking males).24 Furthermore, a significant association was identified between recent
female smoking and the decreased ability to retrieve ova during IVF.24 A second study
examined 221 couples undergoing IVF (aged > 20 years) and found that in couples in which
either member had a positive smoking history, an increased relative risk (2.41) of not
achieving a pregnancy was present (compared with nonsmoking couples).25 This relative
risk was even higher (4.27) among couples that had smoked for > 5 years. This trend
extended to women who had smoked at some point in their lives (adjusted risk of 2.71 for
not achieving a pregnancy).
Joesbury et al26 performed a study on 498 couples undergoing IVF in which the male
partner’s smoking resulted in a significantly lower chance of achieving a 12-week
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pregnancy. These odds of pregnancy were decreased by 2.4% for each additional year of
male age, suggesting that smoking and increasing male age acted in concert to affect fertility
potential. A study of 301 German couples demonstrated that paternal smoking was
associated with significantly reduced success rates for IVF (18% vs 32% in nonsmokers)
and ICSI (22% vs 38% in nonsmokers).27 In fact, logistic regression analyses found that
paternal smoking was a significant risk factor for IVF and ICSI failure, whereas maternal
smoking was a risk factor only for IVF failure. Thus, paternal smoking may play at least as
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A retrospective study of 1770 male European military recruits demonstrated that men who
had prenatal exposure to smoking had a 20.1% lower sperm density as adults than those
recruits without such exposure.28 Men with intrauterine smoking exposure also had modest
but statistically significant reductions in sperm motility and testis size. A more focused
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study on 945 Danish men suggested a trend toward decreasing sperm concentration in adult
men with prenatal exposure to maternal smoking, although the results did not achieve
statistical significance.29 However, the cohort did demonstrate a significantly increased risk
for oligospermia among men whose mothers smoked > 10 cigarettes per day during
pregnancy. Unfortunately, the degree to which this oligospermia translates to male fertility
potential is not known.
A further study by Storgaard et al30 observed that men whose mothers were classified as
high level smokers (i.e. > 10 cigarettes per day) during pregnancy had a 48% lower sperm
density than men who were not exposed to cigarettes in utero. Of note, this association was
not significant in the subset of men whose mothers were in the lower smoking category (i.e.
<10 cigarettes per day during pregnancy), suggesting dose dependence in the relationship
between in utero cigarette exposure and subsequent semen abnormalities.
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limited, this exposure may decrease the likelihood of achieving pregnancy by adversely
affecting both male and female factors.
smoking and infertility. Second, the setting in which patients are selected for the studies are
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critical. For example, examination of the effects of smoking on fertility among men with
infertility and those undergoing vasectomy reversal yields different results, as detailed
above. This dichotomy lends itself to diverse and sometimes conflicting study results.
Nonetheless, evidence supporting an adverse effect of smoking on several key semen
parameters is strong, irrespective of study design. Future studies should attempt to further
elucidate the possible mechanisms in this relationship. Third, many of the studies reviewed
utilize semen analysis parameters as primary end points. Future studies should also
prospectively analyze the impact of smoking on fertility while incorporating successful
pregnancy rates as main outcome measures.
Conclusion
Although a large volume of retrospective data exists examining smoking and the effects on
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semen analysis parameters and IVF outcomes, large-scale, population-wide studies on the
effects of smoking on natural pregnancies are lacking. Nevertheless, the majority of the
evidence points to the fact that men with infertility, or those having difficulty conceiving,
should quit smoking to optimize their chances for successful conception.
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